Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5344
Peer-review started: July 15, 2019
First decision: August 18, 2019
Revised: August 28, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: September 21, 2019
Processing time: 70 Days and 16.8 Hours
The indications for endoscopic submucosal dissection (ESD) have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. However, the risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for early gastric cancer (EGC).
Evaluating the risk of LNM is critical for determining the best course of management for EGC patients. Unfortunately, the risk factors that have been identified in different studies are diverse, and whether patients who met the expanded indications for ESD can be managed safely remains controversial.
We aimed to determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. After working hard on this topic, we have re-evaluated and verified the current indications and guidelines for endoscopic treatment and analyzed the clinicopathological predictors of LNM, which provides strong evidence and reference to future research.
We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. Specifically, we analyzed other clinical features, such as drinking and smoking history, obesity, family history of tumors, and the levels of the tumor marker carcinoembryonic antigen (CEA), which is an innovative aspect of this study.
LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (OR = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. Also, the results of this research affirmed the feasibility of the absolute indications for ESD. However, whether it is reasonable to expand the indications remains to be further discussed.
The absolute indications for ESD can be applied to Chinese patients, while the feasibility of expanding these indications requires further investigation. The predictive factors for LNM included submucosal invasion depth, LVI, mucinous adenocarcinoma, and large lesion size. This study provides clinicians with important reference when evaluating the risk of LNM and determining the best course of management for EGC patients.
Besides invasion depth, LVI, and lesion size, taking the histology of tumors into consideration when deciding upon the ESD indications is vitally important. In addition, preoperative detection of tumor markers is of great necessity. The direction of the future research is to further optimize the ESD indications by analyzing the predictive factors for LNM in EGC. A well-designed multicentric prospective study is the best method for the future research.